Various methods are known for use in sanitization and sterilization in hospitals, operating rooms and the like as well as for other uses such as the treatment of contact lenses.
It is also known, for example, that an oxidizing agent such as chlorine dioxide or hydrogen peroxide can be used, either alone or in combination with other materials, especially those which function as stabilizers for the oxidizing agent when it is in solution.
For example, U.S. Pat. No. 3,082,146 describes the use of stabilized chlorine dioxide for treatment of water and solutions of the same are well known for their excellent bactericidal, fungicidal, and taste and odor control properties. Chlorine dioxide is known for inhibition of slime and algae in the dairy and meat industries, for treatment of industrial wastes and effluents, and for treatment in paper mills, swimming pools, animal pools and the like. Its non-toxicity and ready disappearance with no noxious by-products is a great advantage. Prior to this invention, however, stabilized chlorine dioxide has been incompatible with the eye.
As described in U.S. Pat. No. 4,029,817, hydrophilic plastic materials are used in making soft contact lenses. U.S. Pat. No. 3,503,393 to Seiderman and U.S. Pat. No. 2,976,576 to Wichterle describe processes for producing hydrophilic polymers of polyhydroxyethylmethacrylate in aqueous reaction media having a sparingly cross-linked polymeric hydrogel structure and being elastic, soft, transparent hydrogels. Other soft contact lenses are made of silicone and other suitable materials.
Hydrophilic lenses are particularly useful in opthalmology due to their ability to absorb water and swell to a soft mass of good mechanical strength, and due to their transparency with the ability to retain shape and dimensions when equilibrated in ocular fluid and in storage fluids when removed from the eye.
One problem with soft contact lenses, however, is their sterilization and cleaning. The property of hydrophilic soft lenses which allows them to absorb large amounts of water also allows preservatives which might otherwise be used for cleaning and sterilization to be absorbed and later released onto the eye. The release, furtheremore, may be much slower than the intake, thereby allowing preservatives to build up in the lenses. This can have the harmful result of damaging or staining contact lenses or harming the sensitive tissues of the conjunctivae or cornea. The problems are thoroughly discussed in the articles by J. Z. Krezanoski and R. E. Phares in the Journal of the American Optometric Association, Vol 43, No. 3, Pages 305-313, March, 1972. Furthermore, users of soft contact lenses are warned not to use solutions designed for hard contact lenses, for the reason that the preservatives in such solutions will be absorbed and even concentrated by the soft lens and may seriously damage the soft lenses and/or the eyes of the user upon subsequent transfer from the lenses to the ocular tissue.
As stated by R. E. Phares in U.S. Pat. No. 3,689,673, sterilization of hydrophilic soft contact lenses may be carried out by soaking in an aqueous solution containing approximately 0.001-0.01% chlorhexidine for a time sufficient to sterilize the lens.
Various related methods are disclosed in other U.S. patents. U.S. Pat. No. 3,591,329 discloses the use of a cationic resin exchange material impregnated with active metallic silver. U.S. Pat. No. 3,755,561 teaches using an aqueous solution of polyvinyl pyrrolidone, a polyalkylene glycol and thimerosal. U.S. Pat. No. 3,873,696 discloses using a combination of potassium peroxymonosulfate in the presence of sodium chloride. In U.S. Pat. No. 3,876,768 is described the use of a chlorinated trisodium phosphate material which is similar to hypochlorite. U.S. Pat. No. 3,888,782 relates to the using of chlorhexidine and polyvinyl pyrrolidone. The use of an iodoform solution containing iodine, polyvinyl alcohol and boric acid is disclosed in U.S. Pat. No. 3,911,107. U.S. Pat. No. 3,912,450 proposes using a combination of an alcoholic glutaraldehyde solution containing a surfactant in conjunction with an ultrasonic radiation device.
U.S. Pat. No. 3,888,782 more particularly discloses an aqueous, substantially isotonic cleaning and sterilizing solution for plastic hydrophilic soft contact lenses containing, as active ingredients, chlorhexidine and polyvinylpyrrolidone. The solution is said to be non-toxic to the eye of the wearer of soft contact lenses and in the presence of a suitable amount of water soluble polyhydroxyethylmethacrylate to prevent the build-up of opaque deposits on the surfaces of soft contact lenses.
U.S. Pat. No. 4,029,817 discloses that soft contact lenses may be sterilized by contacting soft lenses with a sterile, aqueous, substantially isotonic solution containing as an active ingredient, an effective amount of a quaternary ammonium compound having the structural formula ##STR1## wherein R represents saturated or unsaturated alkyl residues of fatty acids and mixtures thereof containing from about 12-18 carbon atoms and preferably tallow, A is a non-toxic anion and R.sub.1, R.sub.2, and R.sub.3 are the same or different and represent alkyl radicals having 1-3 carbon atoms; and together with a detoxifying amount of a non-toxic compound selected from the group consisting of water soluble polyhydroxyethyl methacrylate, carboxymethylcellulose, polyoxyethylene sorbitan fatty acids esters, polyoxyethylene alcohols, polyvinylpyrrolidone and mixtures thereof.
Many known quaternary ammonium compounds are generally good bactericides but are also irritating such as, for example, when they come into contact with the eye. Some of these compounds are moreover cationic and can be absorbed by porous surfaces and are difficult to remove. Where these compounds have been made less absorbent, they have never achieved the degree of perfection which would enable their use in critical applications such as with soft contact lenses.
Stabilized chlorine dioxide is known to be a powerful broad spectrum anti-microbial agent, effective in killing gram-positive and gram-negative bacteria, viruses, fungi, etc. The true composition of stabilized chlorine dioxide is an addition compound with the approximate formula of 2Na.sub.2 CO.sub.3.3H.sub.2 O.sub.2.ClO.sub.2. Stabilized chlorine dioxide has long been known as a much more effective anti-microbial agent than chlorine or hypochlorite. It completely consumes bacteria and other micro-organisms thereby preventing the formation of resistant strains. Although stabilized chlorine dioxide is a powerful oxidizing agent, its oxidation potential is less than that of hydrogen peroxide and it does not chlorinate organic compounds. It is purported to have 2.6 times the germicidal power of chlorine, yet it is 10 times as stable in aqueous solution. Stabilized chlorine dioxide is commercially available for a variety of industrial uses. However, it has never been used as an anti-microbial agent for soft contact lenses.
A 5% solution of stabilized chlorine dioxide is colorless, non-corrosive and easy to handle. It can be diluted to any concentration with water. It has government approval for many uses throughout the world. The product is inexpensive and has a long shelf life. The efficacy of stabilized chlorine dioxide increases as the pH value approaches the acid side. It does not have a characteristic chlorine-type odor. Stabilized chlorine dioxide has the unique property of oxygenation without chlorination. It destroys micro-organisms by reaction with cell structure and by speeding up the metabolism to the detriment of cell growth. It prevents immunity build-up. As it is infinitely soluble in water, any occluded chlorine dioxide that would occur within a soft lens could be readily removed by amply washing with distilled water or an isotonic solution. The oxidation potential for chlorine dioxide is ClO.sub.2 +4H.sup.+ +5e.sup.- =Cl.sup.- +2H.sub.2 O 1.50 volts. The oxidation potential for hydrogen peroxide is H.sub.2 O.sub.2 +2H.sup.+ +2e.sup.- =2H.sub.2 O 1.77 volts.
Generally, U.S. Pat. No. 4,073,888 teaches the provision of a cold sterilization product for use on hard surfaces in hospitals, and kitches, for medical instruments, and so forth. At the concentrations described, it is not, however, contemplated for use in disinfecting soft contact lenses, because (1) it would be irritating to the eye and (2) absorption of the quaternary salt in soft lenses would be a major problem.
More specifically, U.S. Pat. No. 4,073,888 relates to a composition of matter which is especially adapted for hard surface, cold sanitization and sterilization especially for killing spores and, more particularly, to aqueous compositions of matter containing chlorine dioxide and certain selected quaternary ammonium salts having the formula ##STR2## wherein R' and R" are alkyl radicals whose total carbon atoms number from 18 to 24, and preferably from 20-22. It is preferred that R' and R" be identical (symmetrical) but this is not necessary although each of the R' and R" radicals should have at least 8 carbon atoms. X is a chlorine, bromine, or any non-toxic non-interfering anion such as is known for the quaternary ammonium salts.
In order to prepare the compositions of U.S. Pat. No. 4,073,888, the chlorine dioxide may be used either in pure form as well as a stabilized chlorine dioxide complex and in solution or suspension either aqueous or non-aqueous in concentrations of from 0.1% to 6.0%. It has been found, according to U.S. Pat. No. 4,073,888, generally necessary to employ one or more emulsifiers for the disclosed compositions. Those emulsifiers are generally linear compounds which are primary alcohol ethoxylates having 12 moles of ethylene oxide and the primary alcohol portion being derived from C.sub.12 -C.sub.15. The optimum range for use in this composition is that the primary alcohol contains from 5 to 12 moles of ethylene oxide, but from 3 to 15 moles are useful. It is believed that the sporicidal activity of these compounds is enhanced by the use of alcohol which of course is not permissible for use in the cleaning of soft contact lenses.
U.S. Pat. No. 4,026,945 discloses synthetic anti-microbial quaternary ammonium copolymers. The copolymers are prepared by the condensation of at least two difunctional tertiary amines using a molar quantity of 1,4-dihalo-2-butene equal to the molar sum of the difunctional tertiary amines in the mixture. The product is disclosed as effective for the anti-microbial treatment of water but is not good for critical applications such as soft contact lenses as mentioned above.
One of the features of the copolymers of U.S. Pat. No. 4,026,945 is that the quaternary ammonium moieties are part of the long polymeric chain rather than being quaternary ammonium moieties on branches that are bonded to the polymeric chain. Another feature is that the copolymer is a unique reaction product and not a mere mechanical mixture of separate polymers. Therefore, the copolymers cannot be separated into constituent components, as would be the case if they were mere mechanical mixtures.
Another feature of U.S. Pat. No. 4,026,945 is that the primary chemical units comprising the polymeric chain are not identically repetitive as they would be if the product were an ordinary polymer. On the contrary, the several primary chemical units of the copolymer are randomly distributed in the polymeric chain.
U.S. Pat. No. 3,428,576 describes polymeric diguanides and their salts which have been found to be effective anti-microbial agents for use with soft contact lenses. These compounds are characterized by the recurring unit ##STR3## where R is a divalent radical, preferably an aliphatic hydrocarbon chain of 4 to 12 carbon atoms, and n is a number such that the molecular weight of the polydiguanide is at least about 800 and upwards to about 12,000, and higher, and preferably from about 1,000 to about 5,000. Salts of these amino/imino polymeric compounds may be made with acids such as hydrochloric acid, sulfuric acid, acetic acid, gluconic acid, etc. A preferred product is the hydrochloric acid salt of poly(hexamethylene diguanide). The product is commercially available from ICI Americas Inc. under the trade name IL-779. This product is an excellent anti-microbial agent, even in the presence of organic matter. It has a low order of toxicity and is chemically stable, non-corrosive, and odor-free. It is effective in concentrations as low as 0.001%.
In accordance with the above-described products, the required characteristics for an effective product are contained in positively-charged, nitrogen-containing cationic polymers, such as the quaternary ammonium compounds described in U.S. Pat. Nos. 4,026,945 and 4,027,020 and the amino and/or imino compounds and their salts, for example, the polydiguanides described in U.S. Pat. No. 3,428,576 as well as U.S. Pat. No. 2,643,232. These types of compounds having a plurality of cationic nitrogen species result in a more potent anti-microbial action, probably because of more points of interaction with the microbial cell wall. The other important factor is the higher molecular weight. The larger polymeric molecules are not as readily absorbed into the hydrophilic lens material, as are the small monomeric molecules.